Oxidative stress and genetic markers of suboptimal antioxidant defense in the aging brain: a theoretical review.
Oxidative stress and genetic markers of suboptimal antioxidant defense in the aging brain: a theoretical review.
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DOI：
10.1515/revneuro-2014-0046
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发表时间：
2014
影响因子：
4.1
通讯作者：
Paul RH
中科院分区：
文献类型：
--
作者：
Salminen LE;Paul RH
正常的衰老涉及生理过程的逐渐崩溃，导致认知功能和大脑完整性的下降，但衰退的开始和进展在老年人中是不同的。虽然许多生物变化可能导致这种程度的可变性，但氧化应激是衰老过程的关键机制，可以直接损害大脑内的细胞结构。由于少突胶质细胞在髓磷脂维持和生成中的作用以及有限的修复机制，它们处于氧化损伤的高风险中，这表明白质可能特别容易受到氧化活性的影响。大脑中的抗氧化防御酶，如超氧化物歧化酶（SOD）、过氧化氢酶（CAT）、谷胱甘肽过氧化物酶（GPx）和谷胱甘肽s -转移酶（GST），对于分解氧化磷酸化的有害最终产物至关重要。先前的研究表明，编码这些抗氧化剂的多态性等位基因变异与中枢神经系统中SOD、CAT、GPx和GST活性异常有关。本文将重点讨论氧化应激在大脑衰老中的作用以及抗氧化防御能力下降对大脑完整性和认知功能的影响。并对今后抗氧化防御基因的研究方向进行了讨论。
Normal aging involves a gradual breakdown of physiological processes that leads to a decline in cognitive functions and brain integrity, yet the onset and progression of decline are variable among older individuals. While many biological changes may contribute to this degree of variability, oxidative stress is a key mechanism of the aging process that can cause direct damage to cellular architecture within the brain. Oligodendrocytes are at a high risk for oxidative damage due to their role in myelin maintenance and production and limited repair mechanisms, suggesting that white matter may be particularly vulnerable to oxidative activity. Antioxidant defense enzymes within the brain, such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione-S-transferase (GST), are crucial for breaking down the harmful end products of oxidative phosphorylation. Previous studies have revealed that allele variations of polymorphisms that encode these antioxidants are associated with abnormalities in SOD, CAT, GPx, and GST activity in the central nervous system. This review will focus on the role of oxidative stress in the aging brain and the impact of decreased antioxidant defense on brain integrity and cognitive function. Directions for future research investigations of antioxidant defense genes will also be discussed.